Neurogenic tumours with an intrathoracic localization - NCBI

Thorax (1968), 23, 374.

Neurogenic tumours with an intrathoraciclocalization

W. M. OOSTERWIJK AND J. SWIERENGA

From the Departmetlts of Lung Diseases and Surgery of the St. Antonius Hospital, Utrecht,The Netherlands

This paper is a clinicopathological review of patients suffering from intrathoracic neurogenictumours.

Neurogenic tumours form one of the mostfrequent anomalies of the mediastinum. In thematerial of our department this diagnosis wasmade in 15% of the patients who had an affectionof the mediastinum. Only intrathoracic and retro-sternal struma occurred with a slightly higherfrequency than neurogenic tumours.The literature contains numerous papers on

intrathoracically localized neurogenic tumours(Kent, Blades, Valle, and Graham, 1944; Blades,1946; Ackerman and Taylor, 1951; Ringertz andLidholm, 1956; Schweisguth, Mathey, Renault,and Binet, 1959 ; Oberman and Abell, 1960 ; Carey,Ellis, Good, and Woolner, 1960; Pachter, 1963;Diane, 1965; Razemon and Ribet, 1965; Dor,Houel, Reboud, Longefait, and Malmejac, 1965;Jaubert de Beaujeu and Maret, 1965; Meyer andOchsner, 1966). Most of these papers concernlimited aspects of such lesions. It therefore seemeduseful to study these tumours in a large series ofcases.The material of St. Antonius Hospital com-

prised the records of 53 patients who had an intra-thoracic neurogenic tumour; with the addition ofmaterial from a few other Dutch hospitals datawere collected forming a total of 111 cases.

EMBRYOLOGY

The nomenclature of neurogenic tumours is con-fusing. To understand the various classificationsused for these tumours requires a knowledge ofcertain aspects of development, because manyneurogenic tumours contain cells derived from

various developmental stages of the nervoussystem. The so-called neural crest is important inthe origin of the peripheral nervous system. Thisregion of the ectoderm situated at the junction ofthe primordium of the neural tube and the restof the ectoderm gives rise, by way of a numberof intermediate stages, to the ganglion cells of thespinal ganglia and the cerebral nerves, theganglion cells of the autonomic nervous system,paraganglionic cells of the sympathetic and para-sympathetic systems, Schwann and satellite cells,and the cells of the pia mater and the arachnoidea(Harvey and Burr, 1926; Stone, 1929; vanCampenhout, 1930; Harrison, 1937; Rawles,1947; Du Shane, 1948; Horstadius, 1950). Sincethese cells often pass through comparable develop-ments, it is not surprising that various neurogenictumours often occur in combination, and thatvarious grades of differentiation occur within onetumour. Many classifications of these tumourshave been made; but the one put forward byStout incorporates almost all of the importantfeatures of the others (Table I).

TABLE ITUMOURS OF THE PERIPHERAL NERVOUS SYSTEM

Benign Malignant

Tumours of the Neurilemmoma Malignant Schwannomaperipheral nerves Neurofibroma (neurogenic sarcoma)

Tumours of the Ganglioneuroma Sympatheticoblastomaautonomous ner- Partly differentiatedvous system ganglioneuroma

Tumours of the Pheochromocytoma Malignant pheochromo-paraganglionic Paraganglioma cytomasystem Malignant paragan-

glioma

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Neurogenic tumours with an intrathoracic localization

MATERIAL AND METHODS

The material comprised the data from Ill patients inwhom a diagnosis of intrathoracic neurogenic tumourhad been made. All the patients had received surgicaltreatment, so that the macroscopical and microscopicalfindings were available. The radiographs and thehistological preparations were re-examined, andfollow-up studies were carried out, in which all thesurviving patients were included.Some of the latter patients were examined post-

operatively, and the remainder either filled in a

questionnaire or were visited at home. The question-naire included questions about complaints that mightbe due to a recurrence and whether chest radiographshad been taken recently. When the thorax had beenexamined either radiologically or fluoroscopicallywithin the year preceding the follow-up, the patientwas registered as having no recurrence.For the patients who had reported themselves to be

free of complaints suggestive of a recurrence of thetumour, it was assumed that there had been norecurrence. Although this did not completely precludethe inclusion of a patient with a recurrence in thisgroup, the chance that this had occurred is, we sub-mit, small.For the deceased patients the cause of death was

determined. Three had died as a result of the opera-tion, one during surgery and two post-operatively.

Eight patients had died within a year of the opera-tion as the result of a recurrence. Data for these wereobtained from the specialists or general practitionersunder whose care they had been.For the patients who had died before the follow-up,

either as the result of a disease unrelated to theneurogenic tumour or of an accident, it could bedetermined from information obtained from thefamily or general practitioner whether complaintshad been present before death that might point to a

recurrence. This was not the case for any of these

patients. Consequently, it may be assumed for thisgroup, too, that there had been no recurrence of thetumour (Table II).

CLINICAL DATA

Although neurogenic tumours occur at all ages,they occur predominantly in young adults. Theymay also be present at birth (Potter and Parrish,1942; Gagnon, Dupal, and Katyk-Longtin, 1962;Mayo, 1963). The average age of the patients inour series was 35 years. The average ages of thepatients with different neurogenic tumours varied:for those with a neurilemmoma it was 40 years;for those with a neurofibroma 37 years; for thosewith a malignant Schwannoma 33 years; and forthose with a neurogenic sarcoma 52 years. Theaverage ages of patients who had a type of neuro-genic tumour originating from the sympatheticnervous system were generally lower. For patientswith a ganglioneuroma, the average age was 20years. Sympatheticoblastoma was most frequentlyseen in children; in our material the average agefor this tumour was 15 years.

The neurogenic tumour in our material occurredwith a slightly higher frequency in women thanin men (59 women; 52 men). This is in agreementwith the data in the literature (Ackerman andTaylor, 1951; Ringertz and Lidholm, 1956; Careyet al., 1960; Diane, 1965; Dor et al., 1965).Neurogenic tumours can occur anywhere where

there is nerve tissue. Despite the fact that nerve

tissue occurs everywhere in the thorax, thesetumours are found predominantly at the site ofthe sympathetic chain and in the path of the spinaland intercostal nerves (Table III).

TABLE IIDATA OBTAINED FROM FOLLOW-UP

No Complaints whenNo. of Checked after (yrs)Patients

1 2 3 4 5 >5

Neurilemmoma 53 I 1 l 72Neurofibroma. 251 32 1 32 42Ganglioneuroma.161 62Pheochromocytoma .. 2 1

Paraganglioma 0Benign tumours.96 1 1 3 2 4 28

Malignant Schwannoma 4

Neurogenic sarcoma 31

Moderately differentiatedganglioneuroma.4 1 3

Sympatheticoblastoma 3 1

Malignant pheochromocytoma 0Malignant peraganglioma ..

Malignant tumours 15 1 4

Total ..I I 1 4 2 4 32

AverageIntervalbetweenTreatment

andCheck-up(years)

107

1046

No Recurrence atCheck-up after (yrs)

1 2 3 4 5 >5

l 6 4 2 193 2 1 7

2 1 6

AverageIntervalbetweenTreatment

andCheck-up(years)

7474942

DeathDueto

Recurrencewithin

yr

9t 5 110 4 4 32 8 0

42

9

7

84 I

9 5 11 4 4 32

3

3 8

8 8

I In this group one patient died as the result of the operation.2 At the time of follow-up, these groups included one patient who had died without having had complaints suggesting a recurrence.

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W. M. Oosterwijk and J. Swierenga

TABLE IIISITE OF NEUROGENIC TUMOURS IN PRESENT STUDY

Neurilemmoma. .NeurofibromaGanglioneuromaPheochromocytoma.Benign tumours

Malignant SchwannomaNeurogenic sarcomaModerately differentiated ganglioneuromaSympatheticoblastomaMalignant paragangliomaMalignant tumours..

Total . . . .

Although few authors mention figures, accord-ing to the literature neurogenic tumours occurwith almost equal frequency on the right and leftsides (Ackerman and Taylor, 1951; Ringertz andLidholm, 1956). In our material there was apredilection for the right side (70 on the rightside, 41 on the left). This predilection was morestrongly expressed in the benign tumours (TableIII).When the neurogenic tumour originated from

the sympathetic chain or the spinal nerve, theclassic localization in the sulcus costovertebraliswas found: this localization was seen in 95 ofour patients. The upper part of the posteriormediastinum was more frequently the origin ofthese tumours than the lower.With a dorsal localization the tumour may

acquire an hourglass shape consisting of an intra-thoracic and an intraspinal (sometimes intradural)portion. Intraspinal extension was seen at surgeryin nine cases, and five showed a stem-like exten-sion reaching as far as the intervertebral foramen.In the pathway of the intercostal nerves a neuro-genic tumour may lie more laterally in the thorax;this was the case in six patients.

In the anterior mediastinum the tumours wereless frequent than in the posterior mediastinum.In this region the lesions can originate from eitherthe phrenic or vagus nerves. In addition to thethree patients in whom the tumour arose from thephrenic or vagus nerves, a localization in theanterior mediastinum was found in four others.In two of these a tumour was removed from theintrathoracic portion of the vagus nerve, and inone from the phrenic nerve. These are unusualsites. Tumours arising from the small nervebranches along the bronchial tree may result in an

intrapulmonary mass; this occurred in threepatients in our series.Neurogenic tumours are usually found by

chance in mass chest surveys or on routine exami-nations for other complaints. Of our 111 patientsthe tumour was found by chance in 94, 77 of theseduring a mass survey and 15 on a routine chestradiograph. Malignant tumours were found bychance in seven patients, although, when a detailedhistory was taken, five were found to have symp-toms. In the group with benign tumours the lesionwas found by chance in 87. Of these, two werefound to have symptoms. The symptoms asso-ciated with neurogenic tumours were varied, andwere often the result of pressure caused by thetumour. The most frequent complaint was pain,which varied in intensity from a vague sensationof pressure to radicular pain. Dyspnoea andcoughing may also occur, and a positive Horner'ssyndrome was found with some tumours in theupper mediastinum.

Neurological signs were seldom evident, prob-ably because of a certain selection: patients withneurological complaints were usually referred tothe neurologist.For the malignant tumours, general complaints

were frequently found in the form of fever and afeeling of being ill. Of the two patients with a

TABLE IV

Benign Malignant To1Tumours Tumours ota

Found by chance .. 87 7 94Found during mass chest survey 75 4 79Found on routine radiography of

the chest .12 3 15No complaints ascribable totumour .85 2 87

Complaints ascribable to tumour I I 13 24Pain.8 10 18Dyspnoea 2 2 4Coughing 2 1 3Positive Horner's syndrome 3 0 3Neurological signs .. 0 1 1General symptoms I.. 3 4Symptoms ofpheochromocytoma I 0

-

l-

376


pheochromocytoma, one showed a complex ofsymptoms due to the biological activity of thisneoplasm (Table IV).

RADIOLOGICAL FINDINGS

Radiography is important in the diagnosis ofneurogenic tumours (Buschmann and Willich,1965; Le Brigand, Merlier, Wapler, Verley, andCarpentier, 1965). A characteristic picture wasgenerally found. On the postero-anterior radio-graph of the thorax the classic case showed a para-mediastinal, usually homogeneous, radiopacitywith sharply defined borders. Medially, this shadowextended into that of the mediastinum. The shapeof the shadow was usually roughly round. Theborders occasionally showed a polycyclic appear-ance. On the lateral radiographs the anomaly wasseen to lie dorsally in the thoracic cavity. Largetumours were partially, and small tumours totally,

projected towards the spinal column. In neoplasmslocated high in the pleural dome the upper limitof the lesion often blended into the shadow ofthe soft tissue of the neck (Figs 1 and 2).The size of the tumour varied from the dimen-

sions of a marble to a very large mass occupyingthe entire thorax (Weiss and Koebele, 1955;Liaras, Houel, and Aprosio, 1956; Lasley, 1957).Tomography in the postero-anterior and lateraldirections made it possible to determine the posi-tion of the tumour exactly with respect to thesurrounding tissue. It also revealed that the locali-zation is not actually mediastinal but in thesulcus costovertebralis.The structure of the tumour can also be seen

more clearly on tomograms. In some it was foundto show lacunae originating from cystic degenera-tion, which could progress so far that a cystseemed to be present. But histological examinationshowed that the wall of the 'cyst' was formed bytissue belonging to the lesion itself.

FIG. 1. Postero-anterior radiograph of the thorax. Paramediastinally located.round, homogeneous radiopacity with sharply defined borders.

377

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FIG. 3. Radiograph after application of a diagnosticFIG. 2. Lateral radiograph. The homogeneous, sharply pneumothorax. The radiopacity is not attached to thedefined shadow is partially projected on the spinal column. collapsed lung.

FIG. 4. Tomogram of the spinal column. There isforamen with erosion of a vertebral bod,.

an enlargement of an intervertebral


Calcification also occurred (Bendixen andLamb, 1926; Bergstrom, 1937; Parsons and Platt,1940; Chandler and Norcross, 1940; Potter andParish, 1942). These calcifications were regarded asregressive changes (Startz and Abrams, 1938;Wyatt and Farber, 1941 ; Mandeville, 1949).Usually, granular calcifications were seen more orless centrally in the tumour mass (Hastings,Pollock, and Snyder, 1961), but some showed ashell-shaped extension of the calcification (Busch-mann and Willich, 1965). Calcification was infre-quent in the intrathoracically localized tumours(Hansman and Girdany, 1957; King, Storaasli,and Bolande, 1961). An extrapulmonary localiza-tion of the tumour could be demonstrated radio-graphically after application of a diagnosticpneumothorax. The usual observation was acollapsed lung to which the tumour was notattached (Fig. 3).We induced a diagnostic pneumothorax in 49

cases; in 46 of these an extrapulmonary localiza-tion could be demonstrated and in three others thiswas probable.

Skeletal radiographs of the thorax were impor-tant for the demonstration of pathological changesin the spinal column and ribs. With an intraspinalextension of the lesion, enlargement of an inter-vertebral foramen could sometimes be found (Fig.4).

If the picture was difficult to interpret, tomo-graphy of the spinal column was useful. Accordingto Ackerman and Taylor (1951), erosion of theribs or vertebrae may be an indication of malig-nancy. But very extensive vertebral changes mayresult in scoliosis; this finding has been reportedby Bobretzkaja and Heinismann (1935), Ackermanand Taylor (1951), Ganz (1954), and Razemon andRibet (1965). According to Love and Dodge(1952), the enlargement of the intervertebral fora-men is the most important sign of intra-spinal ex-tension. They found this enlargement on 40 occa-sions in 60 hourglass tumours. In our material anenlargement of an intervertebral foramen wasfound on the radiograph in two cases; in one'erosion' of a rib was observed.'

Radiologically, investigations such as myelo-graphy may contribute to the determination of theextension of an intrathoracic tumour into thevertebral canal. In some cases angiography, orradiography after the application of a pneumo-peritoneum, may contribute to the differentialdiagnosis.

I Most thoracic surgeons have found 'splaying' of the adjacent ribsto be common.-Editor.

THE DIFFERENTIAL DIAGNOSIS

A large number of anomalies occur in the thoraxand are sometimes difficult to distinguish from aneurogenic tumour. Intrapulmonary lesions suchas hamartochondromas, fibromas, myxomas,lipomas, carcinomas, and metastases were con-sidered when the localization of the neoplasm wasmediodorsal. In most of these cases a diagnosticpneumothorax demonstrated that the localizationwas not extrapulmonary. Mediodorsally localizedbenign pleural tumours, such as fibromas andmesotheliofibromas, seldom gave the impression ofa neurogenic tumour. The same is true for themalignant pleural tumours. Cystic lesions, likebronchial cysts and ecchinococcal cysts, also re-quired consideration. More frequently the distinc-tion concerned lesions localized in the sulcuscostovertebralis or in the posterior mediastinum.For chondromas, osteochondromas, and chondro-sarcomas arising from the ribs or vertebrae, andfor meningocoeles and tuberculous cold abscessesin Pott's disease, a radiological examinationusually provided sufficient information, becausethese lesions almost always involved characteristicchanges in the ribs or vertebrae.

Para-oesophageal cysts, such as gastrogenic,enterogenic, and bronchial cysts, usually layanteriorly. Thoracic struma also entered into thedifferential diagnosis. Difficulties were sometimesencountered, due to pathological changes in theheart or large blood-vessels (e.g., an aneurysm ofthe aorta behind an isthmus stenosis and in anoccasional case of diaphragmatic hernia); anintrathoracically situated lobe of the liver orspleen could give the impression of a neurogenictumour.With the above-mentioned diagnostic methods.

among which radiology was the most important,a diagnosis could be made only with probability.For a definite diagnosis, histological examinationof a biopsy sample or thoracoscopy was required.

PUNCTURE BIOPSY Because the final diagnosis re-quires a histological description of a tumour witha specific structure, we believe that a biopsy issometimes useful. This can be done by punctureof the tumour. This sample consists of only asmall portion of the tumour and may not berepresentative of the whole.

In our material a puncture biopsy was carriedout in 35 cases. In 16 of these tumour tissue wasnot obtained and no diagnosis could be made. Innine, the pathologist could only establish thepresence of a benign or malignant tumour; in onethe conclusion was incorrect. In 10 a diagnosis was

379


TABLE VDIAGNOSES BASED ON PUNCTURE BIOPSIES

made from the puncture material; in eight casesthis diagnosis proved to be correct, in one case aneurilemmoma was mistakenly diagnosed as aneurofibroma, and in one a malignant Schwan-noma was diagnosed as a neurilemmoma (TableV).

1 HORACOSCOPY Thoracoscopy after application ofa pneumothorax can sometimes provide valuableinformation about the morphological aspects ofthe tumour. In the classic case, a yellowish-whitesubpleurally localized mass, sometimes showing acystic appearance, was found in the sulcus costo-vertebralis. A biopsy or puncture sample takenthrough the thoracoscope has been valuable. Anadvantage over percutaneous puncture was that amore suitable portion of the mass could be chosenfor sampling. Increasing use is being made of thisdiagnostic procedure in our hospital. In seven ofthe nine cases with neurogenic tumours in whichthoracoscopy was performed, a definitive diagnosiswas made in this way.

For pheochromocytoma and tumours of thesympathetic nervous system, such as sympathetico-blastoma and ganglioneuroma, determination ofthe catecholamines in the urine was used forreaching a diagnosis (Jacob, 1962; Huebner andReed, 1963; Mathey, Lemoine. Schweisguth,Buhuon, and Labrosse, 1965).

THERAPY

Neurogenic tumours can be treated by surgicalremoval and, in some cases, irradiation or chemo-therapy.The mortality of surgical removal of neurogenic

tumours was low when the mass was not so largethat it caused functional disturbances. In our

material one patient died during surgery and twoshortly after the operation. In the first, death wasdue to a number of factors: it was a large tumourin a patient of advanced age who also had cardiacanomalies. Of the two patients who died shortlyafter the operation, death was caused in one byuraemia due to transfusion from an incompatibleblood group and in the other by haemorrhagicdiathesis of unknown origin.

In 111 patients the mortality rate was just below3%.The post-operative complications associated

with intrathoracic neurogenic tumours varied, buttheir frequency was low. In the literature mentionis made of haemothorax, atelectasis, chylothorax,disturbance of the brachial plexus, and a positiveHorner's syndrome (Binet, Lemoine, Galey, andMathey, 1965). In our material a pleural exudatewas found in four patients, requiring one or moreaspirations. One patient developed empyema post-operatively, and one had a haemothorax aftersurgery requiring a second thoracotomy. Onepatient, in whom a neurogenic tumour with anintraspinal extension was removed by thoraco-tomy, developed a transverse lesion of the cord,probably as the result of pressure from a remnantof the tumour in the vertebral canal. This trans-verse lesion persisted after laminectomy to removethe rest of the tumour. Temporary paresis of thebrachial plexus was observed post-operatively intwo patients.

There were four reasons for surgical treatment:

1. THE RISK OF MALIGNANCY In our material,the diagnosis of malignancy was made in 15 cases,which amounted to almost 14%. Baridty andCoury (1958) report 20% malignant tumours in790 intrathoracic neurogenic tumours collected

380


from the literature. When a definitive diagnosiswas lacking a chance of malignancy of the order of14 to 20% was taken into account.

2. INCREASE IN THE SIZE OF THE TuMOUR This

increased the risk of surgery. We encountered thissituation when a patient died during the operationto remove a very large mass.

3. THE CHANCE OF MALIGNANT DEGENERATION It is

difficult to find exact data on this point in theliterature. Although neurilemmoma is said almostnever to become malignant, malignant degenera-tion has been reported for neurofibromas(Harrington, 1934; Ganz, 1954; Thorsrud, 1960).The percentage of neurofibromas that becomemalignant cannot be estimated, but the possibilityshould be kept in mind. The chance of malignantdegeneration is also difficult to assess becauseganglioneuroma also occurs in combination withsympatheticoblastoma. In these partially differen-tiated ganglioneuromas a biopsy sample may con-

tain only ganglioneuroma tissue, resulting in an

incorrect diagnosis.

4. DANGER OF PERMANENT DAMAGE TO NERVE

S URUCTURES IN SPINAL CANAL WITH INTRASPINAL

EXTENSION OF TUMOUR All forms of neurogenictumour can extend intraspinally. One of ourpatients developed a transverse lesion as the resultof a tumour remnant left behind in the vertebralcanal after excision of the main mass. An intra-spinal extension was found in nine cases, and infive there was extension as far as the intervertebralforamen.A special therapeutic problem arose with respect

to patients suffering from neurofibromatosis (vonRecklinghausen's disease) with an intrathoracicallylocalized tumour. This was usually a neuro-fibroma. According to the literature, the chance ofmalignant degeneration is great in these cases.

Various authors calculate the chance of malignantdegeneration in this group to be of the order of10% (Hosoi, 1931 ; Stout, 1935; Holt and Wright,1948; Preston, Walsh, and Clarke, 1952). Surgicaltreatment has been thought to increase the chanceof malignant degeneration (Hosoi, 1931; Clement,Delon, and Monod, 1942; Herrmann, 1950;Monod, Paillas, Pesle, and Labeguerie, 195 1;Cayla, Thenot, and Coste, 1963), but this is notconfirmed by Thorsrud (1960) and d'Agostino,Soule, and Miller (1963). It seems likely that thebest policy with respect to von Recklinghausen'sdisease is to reserve radical therapy and to restrictsurgery to cases in which there are complaints

demanding removal, and to cases in which thetumour shows rapid growth. Our material includedonly one case of this type; no recurrence wasfound at a follow-up examination two years aftertreatment.

In our patients a postero-lateral thoracotomywas always performed to remove the tumour. Thisincision was found to give good access. When anintraspinal extension was present, it was usuallypossible to remove this part of the tumour by thesame route. When this was not possible, the restof the tumour had to be removed by laminec-tomy at the same operation or shortly thereafter.Laminectomy was required on four occasions. Inthe other five patients who had an intraspinal ex-tension this could be removed at thoracotomy.This was also the case for the five patients inwhom the tumour extended into the intervertebralforamen. When the intraspinal extension has ledto symptoms, it is preferable, according to Ballivet(1949), Merlier (1951), and Love and Dodge (1952),to start with a laminectomy and remove the intra-thoracic portion of the tumour later.

In 96 of our patients a benign tumour wasremoved surgically. Two of these died post-opera-tively due to surgical complications. The follow-upshowed that five patients had died of unrelatedcauses, without evidence of recurrence. In the 89who were still alive at the time of the follow-up,there had been no complaints suggestive ofrecurrence. Ackerman and Taylor (1951), Ringertzand Lidholm (1956) and Carey et at. (1960) alsoreport a very low percentage of recurrence aftersurgery for benign neurogenic lesions.

Patients with a sympatheticoblastoma presenteda special problem of treatment. The evaluation ofthe results of treatment in these is complicated bythe spontaneous recovery that sometimes occurs(Cushing and Wolbach, 1927; Ackerman andTaylor, 1951; Koop, Kiesewetter, and Horn,1955; Bodian, 1959; Eyre-Brook and Hewer,1962; Oberman, 1963; Swaen, 1966). The chanceof spontaneous recovery is greater the youngerthe patient, and amounts to about I to 2% forchildren under I year of age (Hastings et al.,1961). The explanation for the phenomenon isnot clear, and may not always be the same. Incertain cases it may be assumed that the tumourhas become more mature and that a ganglio-neuroma has developed from the sympathetico-blastoma (Cushing and Wolbach, 1927; Farber,1940; Wittenborg, 1950; Fox, Davidson, andThomas, 1959; Phillips, 1953; Kissane andAckerman, 1955; Eyre-Brook and Hewer, 1962:Swaen, 1966). In other cases it seems more prob-

381


able that the tumour has grown too rapidly forits blood supply, as a result of which necrosis hasdeveloped (Farber, 1940; Bodian, 1959).

It is generally accepted that the prognosis of theintrathoracic sympatheticoblastoma is slightlybetter than that of the abdominal forms (Horn,Koop, and Kiesewetter, 1956; Gross, Farber, andMartin, 1959; Bodian, 1959; Hastings et al., 1961;Buschmann and Willich, 1965). Sutow (1958)found no difference in prognosis between the ab-dominal and the other localizations. In infantsthe chance of a cure is greater than in olderchildren (Horn et al., 1956; Gross et al., 1959;Dargeon, 1962; Hastings et al., 1961; Vinik andAltman, 1966).

THE CHOICE OF TREATMENT With respect totherapy, three possible courses, or combinationsof them, are available, namely-surgical removalof the tumour, irradiation, or chemotherapy.

1. Surgical treatment of sympatheticoblastomaswas often difficult because the infiltrative growthof the tumour made radical removal difficult. Ingeneral, the most radical treatment possible wasapplied (Wittenborg, 1950; Gross et al., 1959;King et al., 1961 ; Hastings et al., 1961). Whenradical excision was impossible, it remained impor-tant to remove as much of the tumour as possible.Poore, Dockerty, Kennedy, and Walters (1951)found a survival percentage of 10% for therapyconsisting solely of a biopsy; for the best possibleexcision of the tumour this value rose to 50%. Asimilar observation has been reported by Koopet al. (1955).

2. Irradiation was given in the form of roentgentherapy after surgery. Pre-operative irradiation isrecommended by Buschmann and Willich (1965),but Gross et al. (1959) and Hastings et al. (1961)advise against it.

Wittenborg (1950) used a tumour dose of 800to 1,200 r over 10 to 14 days, followed within threemonths by a second series with the same dosage.Irradiation can be started on the day of the opera-tion (Gross et al., 1959). The danger of post-operative bleeding was not increased by this treat-ment. Buschmann and Willich (1965) advised ahigher dose; they used 2,000 to 3,000 r with radicalresection and 4,000 to 5,000 r with incompleteresection.

Irradiation of metastases is generally consideredto be useful, although it has been found that betterresults are to be expected for metastases in softtissue (liver, etc.) than for skeletal metastases(Wittenborg, 1950; Poore et al., 1951; Uhlmannand von Essen, 1955; Seaman and Eagleton,

1957; Hastings et al., 1961). Cases of skeletalmetastases with recovery are known. According toBuschmann and Willich (1965), 16 such have beenreported in the literature.

3. Chemotherapy has been reported to givereasonably good results (Buschmann and Willich,1965). Satisfactory results have been obtained, forinstance, with cyclophosphamide (Sweeney,Trittle, Etteldorf, and Whittington, 1962;Gurrson, 1963; Weber, 1964; Sawyers et al.,1964; Thurman, Fernbach, and Sullivan, 1964).A somewhat unusual place is occupied by treat-

ment with vitamin B12. The first publications onthis subject by Bodian (1959; 1963) seemed en-couraging. Bodian had treated 74 children, mostof whom had extensive metastases, with highdoses of vitamin B12 (1 mg. every 2 days for 2years; after 1957 1 mg. per 7 kg. body weight for3 years). He reported 33 deaths in this group.Twenty-eight children had been followed for morethan 2 years. The explanation of the effect ofvitamin B12 has not been clarified but could be dueto a growth-promoting effect causing the tumourto exceed the capacity of its blood supply, result-ing in necrosis, or to an influence of the vitaminby which a ganglioneuroma develops from asympatheticoblastoma. Phillips (1953), Fisher(1958), Isaacs, Medalie, and Politzer (1959), andKnudson and Amromin (1966) also report goodresults with this treatment. A questionnairesurvey to collect the results obtained by a groupof American surgeons with vitamin B12 therapy,which concerned 103 patients, yielded no conclu-sive results (Sawitsky and Desposito, 1965).Consequently, a final opinion on treatment withvitamin B12 cannot be given, but, because evenlarge dosages of that vitamin do not have a toxiceffect, it would seem advisable to apply this treat-ment consistently in combination with surgery andirradiation.Our material included three cases of sympathet-

icoblastoma and four of moderately differentiatedganglioneuroma. These patients were treatedsurgically: a macroscopically radical operationcould be performed in seven. High dosages ofvitamin B12 were also administered (2 mg. everyother day). The four patients with moderatelydifferentiated ganglioneuroma had no recurrenceafter 4, 7, 10, and 17 years. Of the three patientswith a sympatheticoblastoma, one died within ashort time; the other two showed no signs ofrecurrence after 3 and 7 years.

Malignant Schwannoma and neurogenic sar-coma have a poor prognosis. The treatments ofchoice are surgery (although a macroscopically

382


radical operation is often impossible) and irradia-tion. Our material included seven of these malig-nant neoplasms. These patients were treated withsurgery and post-operative irradiation; one ofthem died during the operation. The follow-upshowed that all the others had died of a recurrencewithin one year of the operation. These findingsagree with the data in the literature: Ackermanand Taylor (1951), Ringertz and Lidholm (1956),Poole and Deeley (1963), Heard (1963), Cayla etal. (1963), and d'Agostino et al. (1963) also reporta high percentage of recurrence for these tumours.

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d'Agostino, A. N., Soule, E. H., and Miller, R. H. (1963). Sarcomasof the peripheral nerves and somatic soft tissues associated withmultiple neurofibromatosis (von Recklinghausen's disease). Ibid.,16, 1015.

Ballivet, J. (1949). Volumineux neurinome en sablier intrarachidienet intrathoracique. Rev. neurol., 81, 66.

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